Criteria Used to Determine Unrestricted Return to Activity After ACL Reconstruction in Pediatric and Adolescent Patients: A Systematic Review.

Background: The rates of anterior cruciate ligament (ACL) graft failure or contralateral ACL rupture range from 17% to 30% in pediatric patients after ACL reconstruction (ACLR). A contributing factor to the high reinjury rate in this population may be the limited evidence regarding appropriate criteria for allowing unrestricted return to activity (RTA) postoperatively. Purpose: To review the literature and identify the most commonly used criteria when determining unrestricted RTA after ACLR in pediatric patients. Study Design: Systematic review; Level of evidence, 4. Methods: A search was performed of the Medline/PubMed, Cochrane Central Register of Controlled Trials, Embase, CINAHL, and SPORTDiscus databases using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The authors identified studies that included pediatric patients (<19 years of age) and specified the criteria used to determine RTA after ACLR. Results: A total of 27 articles met all criteria for review, of which 13 studies only used 1 criterion when determining RTA. Objective criteria were the most common type of criteria for RTA (17 studies). Strength tests (15 studies) and hop tests (10 studies) were the most commonly used tasks when deriving RTA criteria. Only 2 studies used validated questionnaires to assess the patient's physiological readiness for RTA, and only 2 studies used an objective assessment of movement quality before RTA. Conclusion: Only 14 of the 27 reviewed studies reported using >1 criterion when determining RTA. Furthermore, few studies used patient-reported outcome measures or lower limb kinematics as RTA criteria, indicating that more research is needed to validate these metrics in the pediatric population.

Barriers and Facilitators of Research in Pediatric Sports Medicine Practitioners: A Survey of the PRiSM Society.

Background: Barriers and facilitators to research in sports medicine (SM) by physicians and allied health (AH) professions such as physical therapists and athletic trainers are understudied. The purpose of this research was to examine and compare research barriers, facilitators, and other research related facets including interests, comfort, knowledge, and resources among SM physicians and AH practitioners. Study Design: Cross-sectional survey. Methods: The survey was sent to Pediatric Research in Sports Medicine (PRiSM) members. The survey was designed to ask respondents to identify their top barrier and facilitator to conducting research. Research interest (binary), self-rated comfort reading research articles (0-100 scale), self-rated knowledge conducting research independently (0-100 scale), and available research resources were evaluated. Descriptive statistics, chi-square, and t-tests were used to compare the responses between SM physicians and AH practitioners. The value of p<0.05 was set as a statistically significant criterion. Results: The response rate was 35.7% (N=100). For both SM physicians and AH practitioners, the greatest research barrier was a lack of time. However, the leading research facilitators differed in the two professions. The top research facilitator for SM physicians was availability of research personnel, while availability of research mentoring was selected as a prime facilitator by AH practitioners. There were no differences in research interest between SM physicians (87.0%) and AH practitioners (95.5%, p=0.267). However, self-rated comfort reading research articles was higher in SM physicians (75.6±20.6) than AH practitioners (60.6±28.3, p=0.018). There were no differences in self-rated knowledge conducting research independently between SM physicians (70.2±18.6) and AH practitioners (63.4±24.6, p=0.163). Conclusion: Lack of time was the top research barrier for both SM physicians and AH practitioners. Regarding research facilitators, having available time was the main facilitator for SM physicians while availability of mentoring was the leading facilitator in AH practitioners. Level of Evidence: 3.

Protocol for the systematic review of return-to-activity criteria in adolescent patients following an anterior cruciate ligament reconstruction.

BACKGROUND: Anterior cruciate ligament (ACL) rupture is a debilitating knee injury associated with sequela such as joint instability and progressive degeneration. Unfortunately, following surgical ACL reconstruction in adolescents, the rates of ACL graft failure range from 17 to 19%. A contributing factor to the high reinjury rate in this population may be the limited evidence regarding appropriate criteria for allowing unrestricted return-to-activities (RTA) postoperatively. Several systematic reviews have already sought to develop a consensus on what criteria should be utilized for releasing patients to unrestricted sports activities; however, these reviews have focused on adult populations, a group at much lower risk for reinjury. Our objective is to systematically examine the literature and identify the criteria used when determining unrestricted RTA following an ACL reconstruction in an adolescent population. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search will be performed of the MEDLINE/PubMed, Cochrane, Embase, CINAHL, and SPORTDiscus electronic databases. Searches will be conducted from January 1, 2000, until submission of the final review. Studies will be identified that include adolescent patients (10-18 years old) undergoing a primary ACL reconstruction and which have specified the criteria used to determine RTA. Each article will be independently screened by two reviewers. To supplement the electronic database search, citations within all included studies will be manually reviewed. Reviewers will record the RTA assessment utilized and the rates of ACL reinjury through a standardized data extraction sheet. Reviewers will resolve full-text screening and data extraction disagreements through discussion. Synthesis of the collected data will focus on compiling and mapping the most commonly used types of RTA criteria. DISCUSSION: This systematic review will determine the most commonly used RTA criteria in adolescent patients post-ACL reconstruction. This will help future interventions build more effective adolescent-specific RTA assessments through the validation of current RTA criteria as well as the implementation of new criteria according to the identified literature gaps.

PCR performance in the SARS-CoV-2 Omicron variant of concern?

The new SARS-CoV-2 Omicron variant (B.1.1.529) has been recently declared a Variant of Concern due to a series of important mutations in the viral spike protein and especially in the receptor-binding domain. While investigations into the spread of this new variant are ongoing, the first cases have been detected in Switzerland. Important questions have been raised: (1) Will the PCR assays commonly used to detect SARS-CoV-2 still work for the Omicron variant? (2) Can specific PCR features, e.g. S-gene dropout, be used to identify potential Omicron samples? In this minireview we provide current knowledge on the Omicron variant and guidance on its PCR validation.

Sex differences in muscle activation patterns associated with anterior cruciate ligament injury during landing and cutting tasks: A systematic review.

Neuromuscular control is critical for maintaining dynamic joint stability and mitigating the risk of anterior cruciate ligament (ACL) injury. Given the increased risk of ACL injury in females, sex-based differential muscle activation strategies are often associated with this risk. For example, the quadriceps-dominant muscle activation strategy sometimes observed in females has been discussed as a cause of their increased risk of ACL injury. However, there has been no synthesised knowledge on sex differences in muscle activation patterns associated with ACL injuries. Therefore, the purpose of this review was to synthesise sex differences in muscle activation patterns in movements associated with ACL injuries in both adult and adolescent populations. A systematic electronic database search was conducted. Thirty studies were included in the review. Females demonstrated higher pre- and post-landing activation of the quadriceps and lower activation of the hamstrings in 15 studies. Females also had higher quadriceps-to-hamstring co-contraction ratios during pre- and post-landing phases compared to their male counterparts in 4 of 9 studies that considered co-contraction. While some studies supported the quadriceps-dominant activation strategies in females, no consensus can be drawn due to methodological inconsistencies and limitations. Also, despite the importance of ACL injury prevention in children and adolescents, the evidence on sex difference in muscle activation patterns in this population is insufficient to draw meaningful conclusions.

SARS-CoV-2 N501Y Introductions and Transmissions in Switzerland from Beginning of October 2020 to February 2021-Implementation of Swiss-Wide Diagnostic Screening and Whole Genome Sequencing.

The rapid spread of the SARS-CoV-2 lineages B.1.1.7 (N501Y.V1) throughout the UK, B.1.351 (N501Y.V2) in South Africa, and P.1 (B.1.1.28.1; N501Y.V3) in Brazil has led to the definition of variants of concern (VoCs) and recommendations for lineage specific surveillance. In Switzerland, during the last weeks of December 2020, we established a nationwide screening protocol across multiple laboratories, focusing first on epidemiological and microbiological definitions. In January 2021, we validated and implemented an N501Y-specific PCR to rapidly screen for VoCs, which are then confirmed using amplicon sequencing or whole genome sequencing (WGS). A total of 13,387 VoCs have been identified since the detection of the first Swiss case in October 2020, with 4194 being B.1.1.7, 172 B.1.351, and 7 P.1. The remaining 9014 cases of VoCs have been described without further lineage specification. Overall, all diagnostic centers reported a rapid increase of the percentage of detected VOCs, with a range of 6 to 46% between 25 to 31 of January 2021 increasing towards 41 to 82% between 22 to 28 of February. A total of 739 N501Y positive genomes were analysed and show a broad range of introduction events to Switzerland. In this paper, we describe the nationwide coordination and implementation process across laboratories, public health institutions, and researchers, the first results of our N501Y-specific variant screening, and the phylogenetic analysis of all available WGS data in Switzerland, that together identified the early introduction events and subsequent community spreading of the VoCs.

Sex-specific landing biomechanics and energy absorption during unanticipated single-leg drop-jumps in adolescents: implications for knee injury mechanics.

Females aged between 13 and 17 years old possess the highest non-contact ACL injury incidence of any sex-age strata. Considering that energy absorption strategies have been associated with a reduced risk for sustaining an ACL injury, evaluating landing performance in youth athletes requires investigations beyond the kinematic level. The purpose of this study was to identify sex-specific energy absorption strategies in adolescent males and females, including the relationship between strength and the observed strategies. Thirty-one healthy adolescent athletes completed unanticipated single-leg drop-jump landings on their dominant limb. Sex-specific kinematics and lower-limb contributions to energy absorption were then compared over the landing phase for each jump. Pearson and Spearman correlation coefficients determined the relationship between isometric joint strength and the observed kinematics and energy absorption. Female participants absorbed a larger proportion of the landing energy at the ankle (p = 0.046, d = 0.75) and smaller proportion at the hip (p = 0.028, d = 0.85) compared to males. Females also reached larger peak negative joint power in their knee (p = 0.001, d = 1.1) and ankle (p = 0.04, d = 0.79). Hip extension strength was positively correlated with trunk flexion (r = 0.559, p = 0.001) and negatively correlated with forward pelvic tilt (r = -0.513, p = 0.003). Females adopted an energy absorption strategy which utilized the distal joints to absorb a larger portion of the landing forces and tended to absorb the forces later in the landing phase relative to males. The greater reliance on distal joints is correlated to reduced hip strength and may increase the risk for sustaining an ACL injury.

Decision Tree Learning Algorithm for Classifying Knee Injury Status Using Return-to-Activity Criteria.

Anterior cruciate ligament (ACL) injury rates in female adolescents are increasing. Irrespective of treatment options, approximately 1/3 will suffer secondary ACL injuries following their return to activity (RTA). Despite this, there are no evidence-informed RTA guidelines to aid clinicians in deciding when this should occur. The first step towards these guidelines is to identify relevant and feasible measures to assess the functional status of these patients. The purpose of this study was therefore to evaluate tests frequently used to assess functional capacity following surgery using a Reduced Error Pruning Tree (REPT). Thirty-six healthy and forty-two ACLinjured adolescent females performed a series of functional tasks. Motion analysis along with spatiotemporal measures were used to extract thirty clinically relevant variables. The REPT reduced these variables down to two limb symmetry measures (maximum anterior hop and maximum lateral hop), capable of classifying injury status between the healthy and ACL injured participants with a 69% sensitivity, 78% specificity and kappa statistic of 0.464. We, therefore, conclude that the REPT model was able to evaluate functional capacity as it relates to injury status in adolescent females. We also recommend considering these variables when developing RTA assessments and guidelines.Clinical Relevance- Our results indicate that spatiotemporal measures may differentiate ACL-injured and healthy female adolescents with moderate confidence using a REPT. The identified tests may reasonably be added to the clinical evaluation process when evaluating functional capacity and readiness to return to activity.

Divergence analysis of failed and successful unanticipated single-leg landings reveals the importance of the flight phase and upper body biomechanics.

The purpose of this study was to describe neuromuscular and kinematic differences during failed and successful drop-vertical jumps in a pediatric population. Healthy young athletes (n = 32) completed single-leg drop vertical jump landings where the required landing leg was unanticipated. Trials were categorized as failed if the participant shifted their base of support during the landing. Joint kinematics and muscle activation amplitudes were time normalized over the flight and landing phases. Statistical parametric mapping (SPM) was used to compare landings and a moving average convergence divergence oscillator was then calculated to determine where failed and successful waveforms began to diverge prior to reaching statistical significance. SPM determined that participants performed the failed trials with reduced pelvic tilt towards the landing limb during 41-69% of the flight phase, greater trunk flexion angle during 31-100% of the landing phase and greater trunk tilt away from the landing limb during 3-13% and 21-90% of the landing phase. Greater rectus femoris activation during the failed trials was identified during 88-100% of the flight phase, as well as 1-4% and 71-97% of the landing phase. Greater gluteus medius and biceps femoris activation was also identified in the failed trials during 54-72% and 76-89% of the landing phase respectively. These findings indicate that the control of proximal joints has an important role in determining if a participant will fail a landing; and that how athletes prepare for a landing may be more relevant than the kinematics following ground contact.

Assessing the reporting quality of physical activity programs in randomized controlled trials for the management of juvenile idiopathic arthritis using three standardized assessment tools.

BACKGROUND: The reporting quality of physical activity (PA) programs in randomized controlled trials (RCTs) for the management of juvenile idiopathic arthritis (JIA) remains unknown. This study aimed to assess and compare the reporting quality of PA programs in RCTs for the management of JIA using three difference standardized assessment tools, and to describe the elements that were similar and different between these tools. METHODS: A systematic search was conducted for moderate-to high-quality RCTs of PA programs in JIA, published up until January 2019. Two reviewers independently included 10 RCTs and scored the reporting quality of PA programs using the following tools: Consensus on Exercise Reporting Template (CERT) checklist, Consensus on Therapeutic Exercise Training (CONTENT) scale, and Template for Intervention Description and Replication (TIDieR) checklist. RESULTS: Results showed that reporting of PA programs in 10 moderate- to high-quality RCTs for JIA management remains incomplete. The average reporting quality (± standard deviation) for all RCTs combined was moderate for the three standardized assessment tools with 70.8 (±14.3)% for the TIDieR checklist, 53.2 (±20.2)% for the CERT checklist, and 70.0 (±18.9)% for the CONTENT scale. Despite some overlap, the three standardized assessment tools (TIDieR, CERT, CONTENT) included different elements resulting in different scores. All tools assess elements linked to PA programs (provider, location, timing, personalization and adherence), but the CERT checklist includes other essential elements (e.g., additional resources, motivational strategies, adverse events). CONCLUSIONS: The lack of complete reporting of PA programs in RCTs for the management of JIA and the variation in scores and assessed elements among standardized assessment tools show the need to improve reporting. Using the most comprehensive standardized tool (i.e., the CERT) and providing accessible supplemental information on PA programs may improve the reporting quality of PA programs in RCTs and help reproduce PA programs in research and clinical practice.

Translation and Validation of the Hospital for Special Surgery Pediatric Functional Activity Brief Scale for French Paediatric Populations.

Purpose: Physical activity level is a prognostic variable for patients with injuries. Self-report questionnaires exist to obtain these measures; however, they are not accessible to all populations because of language barriers. Therefore, the purpose of this study was to translate and validate the Hospital for Special Surgery Pediatric Functional Activity Brief Scale (HSS Pedi-FABS) for francophones. Method: We translated the HSS Pedi-FABS using the forward-reverse translation approach and validated it among bilingual adults and an expert panel before administering it to a paediatric population. A repeated-measures crossover design was used: forty-three middle school students, aged 13.1 (SD 0.75) years, were randomly administered either the English or the French questionnaire. Two days later, all participants completed the other version. The translated questionnaire was assessed for its convergent validity (Spearman's r correlation coefficients [rs ]), internal consistency (Cronbach's α), and reliability (standard error of measurement [SEM]). Results: All assessments had a significance level of p < 0.001 with an excellent Spearman's r correlation coefficient between the participants' total scores on the translated questionnaires (rs  = 0.911). The overall scores for the questionnaire and the individual items of the questionnaire revealed excellent internal consistency (α = 0.868) and reliability (SEM = 0.334). Conclusions: The validated and reliable translated questionnaire can be used by researchers and clinicians to assess physical activity levels in French paediatric populations.

Objectif : le niveau d'activité physique est un pronostic variable pour les patients qui présentent des blessures. Il existe des questionnaires d'autoévaluation pour obtenir ces mesures, mais ils ne sont pas accessibles à toutes les populations à cause de la barrière de la langue. La présente étude visait à traduire et à valider le Hospital for Special Surgery Pediatric Functional Activity Brief Scale (HSS Pedi-FABS) pour les francophones. Méthodologie : les chercheurs ont traduit le HSS Pedi-FABS au moyen du processus de rétrotraduction et l'ont validé auprès d'adultes bilingues et d'un groupe d'experts avant de l'utiliser auprès d'une population pédiatrique. Ils ont utilisé une méthodologie transversale par mesures répétées : 43 élèves du début du secondaire de 13,1 ans (ÉT 0,75) ont répondu au hasard au questionnaire anglais ou français. Deux jours plus tard, tous les participants ont rempli l'autre version. Les questionnaires traduits ont été évalués pour leur validité convergente (coefficients de corrélation Rho de Spearman [rs ]), leur cohérence interne (coefficient alpha [α] de Cronbach) et leur fiabilité (erreur type de mesure). Résultats : toutes les évaluations présentaient un seuil de signification de p < 0,001 et un excellent coefficient de corrélation Rho de Spearman entre les scores totaux des participants dans les questionnaires traduits (rs  = 0,911). Les scores totaux du questionnaire et de chacun de ses éléments ont révélé une excellente cohérence interne (α = 0,868) et une excellente fiabilité (erreur type de mesure = 0,334). Conclusion : le questionnaire validé et traduit avec fiabilité peut être utilisé par les chercheurs et les cliniciens pour évaluer les niveaux d'activité physique de populations pédiatriques francophones.

A study of the description of exercise programs evaluated in randomized controlled trials involving people with fibromyalgia using different reporting tools, and validity of the tools related to pain relief.

RATIONALE:: Exercise programs for the management of fibromyalgia are well recognized as being effective. However, the incomplete descriptions of exercise programs make replication and implementation difficult. Also, existing reporting tools have not been validated in relation to pain relief as well as with each other. OBJECTIVES:: This study aimed to evaluate the description of exercise programs in randomized control trials for the management of fibromyalgia using different assessment tools, and the correlations of each tool in relation to effectiveness of pain relief of fibromyalgia, and the correlations between each tool. METHOD/RESULTS:: Through a consensus made by two different pairs of reviewers and an arbitrator, the mean total scores for the exercise programs were reported: 10.61/19 for Consensus on Exercise Reporting Template; 4.17/12 for Template for Intervention Description and Replication; 7.05/12 for the Consensus on Therapeutic Exercise Training; and 2.50/4 (aerobic) and 2.36/5 (flexibility and resistance) for the 2016 American College of Sports Medicine guidelines. This demonstrates generally low reporting scores (less than 60% out of the total number of items were reported). Overall, low correlations (Cohen's kappa value, ranging from -0.47 (poor) to 0.313 (fair)) were found between all tools and pain relief. Good to excellent correlations (0.680-0.908) among the reporting tools were shown. CONCLUSION:: Incomplete descriptions of exercise programs were consistently shown among the randomized clinical trials assessed in this study. The overall weak correlations demonstrated that the reporting tools have the limited ability to determine whether exercise programs were or were not effective for pain relief among individuals with fibromyalgia.

A hierarchy in functional muscle roles at the knee is influenced by sex and anterior cruciate ligament deficiency.

BACKGROUND: Sex-related neuromuscular differences have been linked to greater risk of anterior cruciate ligament injuries in females. Despite this, it remains unclear if sex-related differences are present after injury. This study sought to determine if sex differences are present in the functional roles of knee joint muscles in an anterior cruciate ligament deficient population. METHODS: An isometric, weight-bearing, force-generation protocol required injured and healthy males and females to modulate ground reaction forces. Electromyography was used to classify the functional role of 10 lower limb muscles in their contribution to knee joint stability during various loading directions. These roles were compared between the four groups at 12 loading directions using a directional analysis. FINDINGS: Functional muscle roles were different between groups, except for injured males and healthy females. Healthy males had either joint actuators or specific joint stabilisers, but no general stabilisers; the vastus medialis and lateralis of injured males and healthy females were classified as general stabilisers while injured females added the gluteus medialis and medial gastrocnemius as general stabilisers. INTERPRETATION: A population-based hierarchy in functional muscle roles was discovered. Healthy males demonstrated the most specific muscle roles, which can be viewed as more adaptive to variable loading conditions. The more generalised stabilisation strategies seen in injured males and females would alter joint loading which may be detrimental to the knee joint health over time. In summary, (1) these injuries alter muscle roles; (2) these alterations are sex-specific; (3) rehabilitation might be optimised if sex-differences are considered.

Assessment of the content reporting for therapeutic exercise interventions among existing randomized controlled trials on knee osteoarthritis.

Purpose/Rationale: Physical exercise interventions for the management of knee osteoarthritis are well known to be effective and accessible forms of rehabilitation and symptom management. However, without adequate reporting of these interventions, accurate replication and clinical use is negatively impacted. OBJECTIVES: The main objective of this article was to assess content reporting using The Consensus on Exercise Reporting Template list and 2016 American College of Sports Medicine guidelines among moderate- to high-quality exercise interventions randomized controlled trials (total score of ≥6/10 on the PEDro scale) involving individuals with knee osteoarthritis. RESULTS: The Consensus on Exercise Reporting Template mean total score for all 47 included randomized controlled trials was 4.42 out of 19, demonstrating generally low quality of reporting. The Consensus on Exercise Reporting Template list and the 2016 American College of Sports Medicine guidelines scores were moderately correlated (based on 95% confidence interval, intraclass correlation coefficient = 0.508) for aerobic interventions only. CONCLUSION: The content analysis of exercise interventions in knee osteoarthritis demonstrated low scores for moderate- to high-quality trials. Improved standardized reporting is recommended to ensure knowledge transfer and replication of effective exercise programs for individuals with knee osteoarthritis.

Effect of limb dominance and sex on neuromuscular activation patterns in athletes under 12 performing unanticipated side-cuts.

Non-contact ACL injuries are one of the most common injuries to the knee joint among adolescent/collegiate athletes, with sex and limb dominance being identified as risk factors. In children under 12years of age (U12), these injuries occur less often and there is no sex-bias present. This study set out to explore if sex and/or limb dominance differences exist in neuromuscular activations in U12 athletes. Thirty-four U12 males and females had six bilateral muscles analyzed during unanticipated side-cuts. Principal component analysis was performed, capturing differences in overall magnitudes and timing of peak magnitudes. Two-way mixed-model ANOVAs determined significant limb effects with both sexes displaying (i) greater magnitudes in the lateral gastrocnemius and both hamstrings in the dominant limb and (ii) earlier timing of peak magnitudes in both gastrocnemii, both hamstrings and vastus medialis in the non-dominant limb, while no sex differences were identified. This study demonstrated that limb dominance, not sex, affects neuromuscular activation strategies in U12 athletes during unanticipated side-cuts. When developing injury prevention programs for younger athletes, an increased focus on balancing neuromuscular activations in both limbs could be beneficial in reducing the likelihood of ACL injuries in these athletes as they mature through puberty.

Influenza vaccination given at least 2 weeks before delivery to pregnant women facilitates transmission of seroprotective influenza-specific antibodies to the newborn.

BACKGROUND: Pregnant women and infants are at higher risk of complications secondary to influenza infection. Immunization during pregnancy facilitates protection of the neonates through passive transfer of maternal antibodies. METHODS: This was a cross-sectional study performed during the post-H1N1 pandemic winter season of 2010/2011 in Geneva, Switzerland. We measured antibody titers against the seasonal influenza A H1N1, H3N2 and B 2010/2011 strains by hemagglutination inhibition in the umbilical cord blood of newborns born to vaccinated and nonvaccinated mothers. Seroprotection was defined as a hemagglutination inhibition titer ≥ 40. RESULTS: A total of 188 women were enrolled, 101 of whom had been vaccinated with a nonadjuvanted influenza vaccine (all during the second or third trimester) and the other 87 had not. Among newborns of vaccinated women, 84-86% showed seroprotective levels depending on the strain. In comparison, seroprotection rates were significantly lower in babies of nonvaccinated women (29-33%, P < 0.001). Adjusting for various confounding factors and applying multivariate regression analysis, vaccination during pregnancy ≥ 2 weeks before delivery increased geometric mean titers in umbilical cord blood 5-17 times and seroprotection rates 5.8-34.4 times, depending on the strain and the interval between vaccination and delivery. Vaccinating pregnant women only 2-4 weeks before delivery was still more effective than no vaccination at all (geometric mean titers increased 6.8-11.1 times and seroprotection rates increased 5.8-34.4 times compared with nonvaccinated women). CONCLUSIONS: Influenza vaccination at any time during the second and third trimester of pregnancy, but at least 15 days before delivery, confers seroprotection to many neonates.

Higher memory responses in HIV-infected and kidney transplanted patients than in healthy subjects following priming with the pandemic vaccine.

BACKGROUND: Memory responses require immune competence. We assessed the influence of priming with AS03-adjuvanted pandemic vaccine (Pandemrix®) on memory responses of HIV patients, kidney recipients (SOT) and healthy controls (HC). METHOD: Participants (HIV: 197, SOT: 53; HC: 156) were enrolled in a prospective study and 390/406 (96%) completed it. All had been primed in 2009/2010 with 1 (HC) or 2 (patients) doses of Pandemrix®, and were boosted with the 2010/2011 seasonal influenza vaccine. Geometric mean titres and seroprotection rates were measured 12 months after priming and 4 weeks after boosting. Primary and memory responses were directly compared in 191 participants (HCW: 69, HIV: 71, SOT: 51) followed during 2 consecutive seasons. RESULTS: Most participants (HC: 77.8%, HIV: 77.6%, SOT: 66%) remained seroprotected at 12 months post-priming. Persisting A/09/H1N1 titers were high in HIV (100.2) and HC (120.1), but lower in SOT (61.4) patients. Memory responses reached higher titers in HIV (507.8) than in HC (253.5) and SOT (136.9) patients. Increasing age and lack of HAART reduced persisting and memory responses, mainly influenced by residual antibody titers. Comparing 2009/2010 and 2010/2011 titers in 191 participants followed for 2 seasons indicated lower post-2010/2011 titers in HC (240.2 vs 313.9), but higher titers in HIV (435.7 vs 338.0) and SOT (136 vs 90.3) patients. CONCLUSIONS: Priming with 2 doses of Pandemrix® elicited persistent antibody responses and even stronger memory responses to non-adjuvanted seasonal vaccine in HIV patients than 1 dose in healthy subjects. Adjuvanted influenza vaccines may improve memory responses of immunocompromised patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01022905.

Responses of solid organ transplant recipients to the AS03-adjuvanted pandemic influenza vaccine.

BACKGROUND: Solid organ transplant (SOT) recipients are a priority group for influenza vaccination and strategies enhancing immunogenicity are needed. METHODS: We determined adverse reactions, changes in biomarkers of graft function and immune responses to two doses of the AS03-adjuvanted influenza A/09/H1N1 vaccine in 216 SOT recipients and in 138 controls after one dose. Antibody responses were measured by haemagglutination inhibition and confirmed by microneutralization. We calculated geometric mean titres (GMT) and seroprotection rates (GMT≥40). RESULTS: Adverse reactions were fewer than in controls and graft function remained unaffected. Seroprotection was achieved by only 70.3% of SOT recipients, with significant differences between groups (lung 43.6%, heart 72.0%, kidney 83.3%, liver 83.3% and pancreas 85%), compared to 87% of controls (P<0.001). The weakest responses (seroprotection 43.5%) were elicited in lung transplant recipients. GMT remained threefold lower (115 versus 340) in SOT recipients than controls. Multivariate analyses identified increasing age, type of transplant and increasing blood levels of mycophenolate as independently associated to weaker responses. In contrast, even high blood levels of calcineurin inhibitors remained without significant influence on vaccine responses. CONCLUSIONS: The squalene-based adjuvanted A/09/H1N1 vaccine was safe in SOT recipients. However, even two doses of this adjuvanted influenza vaccine did not provide adequate protection for lung transplant recipients and those with high mycophenolate blood levels. Additional prophylactic measures should, therefore, be considered for these high-risk groups.

A prospective study of the factors shaping antibody responses to the AS03-adjuvanted influenza A/H1N1 vaccine in cancer outpatients.

PURPOSE: To identify the determinants of antibody responses to adjuvanted influenza A/H1N1/09 vaccines in a cohort of cancer outpatients. PATIENTS AND METHODS: Patients with cancer and controls were enrolled in a prospective single-center field study. Two doses of AS03-adjuvanted pandemic influenza vaccine were administered to patients and one dose was administered to controls. Antibody responses were measured using hemagglutination inhibition and confirmed by microneutralization. Geometric mean titers (GMTs) and seroprotection rates (defined as GMTs ≥40) were compared. RESULTS: Immunizations were safe and well tolerated in 197 cancer patients (lymphoma, 57; glioma, 26; lung or head and neck, 37; gastrointestinal, 41; breast, 36) and 138 controls. Similar seroprotection rates (82.3% versus 87%) and GMTs (336.9 versus 329.9) were achieved after two doses of adjuvanted vaccine in cancer patients and one dose in controls. Univariate analyses identified older age, prior immunization against seasonal influenza, lymphoma, CD4 count, active chemotherapy, and rituximab and steroid treatments as being associated with weaker antibody responses. However, only age and chemotherapy plus rituximab remained independent determinants of vaccine responses in multivariate analyses. CONCLUSIONS: Two doses of AS03-adjuvanted influenza vaccine elicited potent antibody responses in most cancer patients despite ongoing chemotherapy, with the exception of rituximab-induced B-cell depletion. Oncology patients treated in an outpatient setting benefit from preventive vaccination against influenza with adjuvanted vaccines.